The present invention relates to method and apparatus for forming ions from a liquid for use by an analytical instrument, typically a mass spectrometer.
Various types of ion sources have been used in the past to produce ions from a liquid for mass spectrometers. Over the last decade the practise has been to produce the ions at or near atmospheric pressure and then to direct the ions into a vacuum chamber which houses the mass spectrometer. Examples of these ion sources include the well known electrospray ion (ESI) source, discussed in U.S. Pat. No. 4,842,701 to Smith et al. and the ion source referred to as ion spray, described in U.S. Pat. No. 4,935,624 to Henion et al.
In its most basic form, an ESI source is created by applying a potential difference on the order of 5000 volts between a metal capillary and an interface lens in which there is an aperture. The distance between the capillary tip and lens is in the range of 1 to 3 centimeters. The analyte is contained in a solvent which is pumped through the capillary. As the liquid emerges from the capillary tip, the high electric field causes charge separation and a subsequent rapid increase of the charged liquid flow velocity accompanied by a sharp reduction of liquid flow diameter, and assuming a shape called a Taylor cone. Within a short distance of the capillary tip, the mutual charge repulsion within the liquid exceeds the ability of the surface tension to contain the liquid, resulting in a scattering of the smooth liquid flow into liquid droplet form. The maximum flow rate of the ESI source is about 5 microliters/minute (xcexcL/m). Much higher flow rates cause the ion signal to decrease and become unstable because of the advent of larger droplets which take too long to desolvate. Consequently much of the ion current becomes bound up in droplets instead of gas phase ions. ESI sources are typically operated at or near atmospheric pressure, because a high heat transfer rate to the droplets required for evaporation is possible due to the high rate of droplet-air molecule collisions.
Prior art ion spray devices can include a concurrent flow of high velocity gas coaxial with a capillary tube. This gas nebulizes the liquid flowing from the capillary tip, effectively resulting in smaller sized droplets. Adding an external source of heated gas results in the effective evaporation of liquid flow up to 1000 microliters per minute.
In some configurations of ion spray or electrospray sources, the metal capillary has been replaced by a nonconductive capillary such as fused silica. The electrical connection to the liquid is usually made at a metal junction upstream from the capillary tip and relatively close to the tip (e.g. 10 cm).
Although ion spray has replaced electrospray in the flow range from about 1 microliter/minute to 1000 microliter/minute, ESI sources called xe2x80x9cnanosprayxe2x80x9d which use extremely low flows of the 1 to 20 nanoliters per minute range are becoming popular for situations where the amount of sample is limited. The nanospray source is distinguished from the higher flow rate sources by having a smaller capillary diameter, and both a lower distance and potential difference between the capillary tip and the lens. The small nanospray capillary bore produces small droplets which quickly evaporate. For example, a typical nanospray source is placed at a distance of between 1 and 3 millimeters from the lens and a typical electrospray source is placed at a distance of between 1 to 2 centimeters from the lens. In addition, due to the very low flow rate of the nanospray source, a large fraction of the ion current from the capillary passes through the aperture of the lens, whereas for the high flow sources, this same fraction is often less than one percent. In both cases, the ion current through this lens aperture is predominantly in the form of desolvated gas phase ions, that is, not in liquid form.
Regardless of the source design, the sensitivity of all atmospheric source designs generally increases with a larger aperture in the lens. Larger apertures are increasingly used to collect more ion current emerging from the capillary, but with a typical fixed ion/gas ratio of ions and gas through the lens aperture, more gas is present which necessitates higher capacity and costly vacuum pumps to maintain the mass spectrometer vacuum pressure. A typical ion/gas ratio for the atmospheric sources is from one ion in 109 to 1010 molecules of air, usually nitrogen.
Attempts have been made to increase the number of ions that can be delivered to a low pressure region by providing electrospray directly into a low pressure region as disclosed in U.S. Pat. No. 5,838,002 to Sheehan, where a potential difference is applied across an electrospray capillary positioned in an evacuated chamber of less than 13 pascals and a counter electrode. This approach is limited by corona discharge which can produce chemical noise, and liquid boiling which disturbs the Taylor cone and causes severe signal instability and signal reduction.
Accordingly, there is a need for a method and apparatus for providing an improved flow of ions into vacuum from an electrospray source such that a low volume of gas is admitted into the vacuum chamber along with the ions, such that corona effects are avoided, such that boiling does not occur, and such that the lab footprint of requisite pumping equipment is reduced.
It is therefore an object of the present invention to provide an apparatus for providing gas phase ions in a relatively low pressure region from a liquid, the apparatus comprising:
(a) a capillary tube, said capillary tube having an input for receiving the liquid, a longitudinal bore, and an outlet for discharging said liquid at a preset flow rate into a first region at a relatively high pressure;
(b) a first interface element with an aperture therein and separating said first region from a second region at a relatively low pressure;
(c) an electrode located downstream from the aperture of the capillary tube; and
(d) a voltage source for generating a voltage potential between said liquid in the capillary tube and said electrode;
wherein the aperture of the capillary tube is aligned with the aperture of the first interface element and is positioned directly in front of, and in close proximity to, the aperture of the first interface element, whereby, in use, with a sufficient voltage potential applied between the liquid and the electrode to form an electric field sufficient to cause the liquid stream flowing through the outlet of the capillary tube at the preset flow rate to become a charged liquid stream that originates at the aperture of the capillary tube and flows through the aperture of the first interface element into the second region and substantially desolvates into gas phase ions in the second region, and wherein the spacing between the aperture of the capillary tube and the aperture of the first interface element is such that there is minimal expansion of the liquid charge stream in the first region.
In a second aspect, the present invention provides an apparatus for providing gas phase ions in a relatively low pressure region from a liquid including a matrix material, the apparatus comprising:
(a) a capillary tube, said capillary tube having an input for receiving the liquid, a longitudinal bore, and an outlet for discharging said liquid at a preset flow rate into a first region at a relatively high pressure;
(b) pulsing means coupled to the capillary tube for providing a series of pressure pulses to the liquid within the capillary tube to cause said capillary tube to expel a series of liquid charge stream droplets;
(c) a first interface element with an aperture therein and separating said first region from a second region at a relatively low pressure;
(d) desolvation means for desolvating the liquid charge stream droplets into gas phase ions in the second region;
wherein the aperture of the capillary tube is aligned with the aperture of the first interface element and is positioned directly in front of, and in close proximity to, the aperture of the first interface element, whereby, in use, when said pulsing means provides sufficient pulsing action to the capillary tube to cause the liquid stream flowing through the aperture of the capillary tube at the preset flow rate to become a pulsed liquid stream that originates at the aperture of the capillary tube and flows through the aperture of the first interface element into the second region, said desolvation means interacts with said matrix material to create reagent ions and to substantially desolvate said pulsed liquid stream into gas phase ions in the second region, and wherein the spacing between the aperture of the capillary tube and the aperture of the first interface element is such that there is minimal expansion of the liquid stream in the first region.
The present invention also provides a number of other features which can be provided either instead of, or in combination with the feature recited in the preceding paragraph (mounting the capillary tube in a manner such that the liquid charge stream flows through into the second region without substantially desolvating). These features include:
(1) locating the outlet of the capillary tube relative to the aperture and dimension of the aperture such that substantially all of the liquid ion current passes through into the second region, whereby only a small or negligible ion current is detected on the first interface element, i.e. a current which is orders of magnitude less than the ion current flowing into the second region;
(2) providing a diameter for the bore of the capillary tube, at the outlet thereof, in the range of 12-125 micrometers, mounting the outlet from the aperture at a distance in the range 50 to 500 micrometers and providing the aperture with a diameter in the range of 5 to 500 micrometers.
(3) mounting the tip of the capillary tube, including the capillary tube outlet, in a cap, the cap including the aperture and the cap serving to locate the outlet of the capillary tube both axially and radially relative to the aperture, wherein the first interface element includes a bore within which the cap is mounted.
(4) while reference has been made to the use of a capillary tube within the ion source apparatus, it should be understood that instead of using a capillary tube to introduce liquid analyte into the ion source chamber, it would be possible to use any means of introducing a source of liquid analyte into the ion source chamber instead of using a capillary tube.
In a third aspect, the present invention provides a method of forming gas phase ions in a relatively low pressure region from a liquid, the method comprising the steps of:
(a) directing the liquid through a capillary tube having an outlet to provide a liquid stream at a preset flow rate into a first region at a relatively high pressure;
(b) providing an electrode downstream from the aperture;
(c) providing a first interface element including an aperture and separating the first region from a second region at a relatively low pressure;
(d) positioning the capillary tube such that the outlet of the capillary tube is aligned with the aperture of the first interface element and is positioned in front of, and in close proximity to, the aperture of the first interface element;
(e) applying an electric potential between the liquid within said capillary tube and the electrode to form an electric field, sufficient to cause said liquid stream to form a charged liquid stream, whereby the charged liquid stream originates at the outlet of the capillary tube and flows through the aperture of the first interface element into the second region; and
(f) locating the outlet of the capillary tube at a distance from the aperture such that there is minimal expansion of the charged liquid stream in the first region and such that substantially all the liquid passes through the orifice, for vaporization in the second region.
In this third aspect of the invention, it is envisaged that, step (f) and, where applicable step (e), could be replaced or combined with one or more of the following features:
(1) causing substantially all the ion current to pass through the aperture, whereby only a relatively small ion current is detected at the interface element;
(2) spacing the outlet of the capillary tube in the range 50 to 500 micrometers from the aperture, and/or providing the outlet of the capillary tube with a diameter in the range of 12 to 125 micrometers, and/or providing the aperture with a diameter in the range of 5 to 500 micrometers;
(3) locating the aperture such that the jet region of the Taylor cone extends through the aperture, or locating the aperture such that at least a portion of the plume region is located in the aperture and may extend, at least partially, into the first region; and
(4) causing at least 90% of the sample to pass through the aperture into the second region.
In a fourth aspect, the present invention provides a method of forming gas phase ions in a relatively low pressure region from a liquid containing a matrix material, the method comprising the steps of:
(a) directing the liquid through a capillary tube having an outlet to provide a liquid stream at a preset flow rate into a first region at a relatively high pressure;
(b) providing a first interface element including an aperture and separating the first region from a second region at a relatively low pressure;
(c) positioning the capillary tube such that the outlet of the capillary tube is aligned with the aperture of the first interface element and is positioned in front of, and in close proximity to, the aperture of the first interface element;
(d) applying pressure pulses to the capillary tube to cause said capillary tube to expel a series of liquid charge stream droplets to cause the liquid stream flowing through the aperture of the capillary tube to become a pulsed liquid stream that originates at the aperture of the capillary tube and flows through the aperture of the first interface element into the second region;
(e) locating the outlet of the capillary tube at a distance from the aperture such that there is minimal expansion of the charged liquid stream in the first region and such that substantially all the liquid passes through the aperture, for vaporization in the second region; and
(f) desolvating said droplets into gas phase ions in the second region.
Further objects and advantages of the invention will appear from the following description, taken together with the accompanying drawings.